Friday, May 16, 2014

Food therapy - Avocado

Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae.
Nutrients
1. Vitamin K
2. Dietary fiber
3. Vitamin B6
4. Vitamin C
5. Folate
6. Copper
7. Potassium
8. Amino acid
9. Others
a) Vitamin A
b) Vitamin B1, B2, B3, B12
c) Vitamin D
d) Vitamin E
e) Carotenoid
f) Pantothenic acid
g) Calcium
h) Chromium
Chemical constituents
The fruit contains campesterol, high amounts of β-sitosterol (average 76.4 mg/100 g); fatty acids (approximately 60% monounsaturated, 20% saturated, and 20% unsaturated); high amounts of glutathione (27.7 mg/100 g); approximately 2% protein; 6–9% carbohydrates and sugars (glucose, fructose, d-mannoheptulose, a taloheptulose, and an alloheptulose); two bitter substances (1-acetoxy-2,4-dihydroxyheptadeca-16-ene and 1,2,4-trihydroxyheptadeca-16-ene); carnitine; proanthocyanidins; persenones A and B(a).

1. Avocado and leukemia
Hass avocados, the most common commercial avocado cultivars in the world, not only support the  cardiovascular health also process the properties in maintaining healthy weight  and healthy aging(1).
Endocarp, seed, whole seed, and leaf (0.1 mg/mL) extracts showed to inhibit leukemic cell profileration through an oxidative stress mechanism, according to the University of Antioquia(2)

References
(a) Leung's Encyclopedia of Natural Ingredients:Chemical Composition of Avocado
(1) Hass avocado composition and potential health effects by Dreher ML1, Davenport AJ.(PubMed)
(2) Pro-apoptotic effect of Persea americana var. Hass (avocado) on Jurkat lymphoblastic leukemia cells by Bonilla-Porras AR1, Salazar-Ospina A, Jimenez-Del-Rio M, Pereañez-Jimenez A, Velez-Pardo C.(PubMed)
(3)

2. Avocado and Cholesterol
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood. The special particle called lipoprotein moves this waxy, soft substance from place to place.
Avocado may be one of best fruit used to reduced the accumulation of bad cholesterol in the blood, as it process body fat lowering capacity. The fruit was also found to reduced risk of metabolic syndrome(1), including obesity(2) and cardiovascular diseases(3) According to Dr. Monika P, and Dr. Geetha A., hydro-alcoholic fruit extract of P. americana (HAEPA) in a  a period of 14 weeks rat study, showed a significantly decreased body mass index (BMI), total fat pad mass and adiposity index. Levels of reduced glutathione, adiponectin, mRNA expression of adiponectin were significant lower in rat in rats fed a high-fat diet (HFD)(4). The study of the level of expression of adiponectin and PPAR-γ in rats, Persea americana (avocado) fruit extract enhanced the HAEPA exhibition of hypolipidemic activity probably by increasing the mRNA, which is RNA messenger expression of adiponectin, a protein with function in regulating glucose levels as well as fatty acid breakdown. and PPAR-γ, a protein with function in regulation of cellular metabolism (carbohydrate, lipid, protein), and tumorigenesis, which reduce the risk of hyperlipidemia and obesity(5). In support od the view of above, researchers at the Potchefstroom University for Christian Higher Education, suggested that consumption of 200 g/d of avocado within an energy-restricted diet does not compromise weight loss when substituted for 30 g of mixed dietary fat. Serum lipid concentrations, plasma fibrinogen, arterial compliance, and systolic and diastolic blood pressures were not affected by weight loss or avocado intake(6).

References
(1) Avocado consumption is associated with better diet quality and nutrient intake, and lower metabolic syndrome risk in US adults: results from the National Health and Nutrition Examination Survey (NHANES) 2001-2008 by Fulgoni VL 3rd1, Dreher M, Davenport AJ.(PubMed)
(2) Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-γ in rats subjected to experimental hyperlipidemia and obesity by Monika P, Geetha A.(PubMed)
(3) Avocado oil supplementation modifies cardiovascular risk profile markers in a rat model of sucrose-induced metabolic changes by Carvajal-Zarrabal O1, Nolasco-Hipolito C2, Aguilar-Uscanga MG3, Melo-Santiesteban G4, Hayward-Jones PM1, Barradas-Dermitz DM5.(PubMed)
(4) Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-γ in rats subjected to experimental hyperlipidemia and obesity by Monika P, Geetha A.(PubMed)
(5) Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-γ in rats subjected to experimental hyperlipidemia and obesity by Monika P, Geetha A.(PubMed)
(6) Substitution of high monounsaturated fatty acid avocado for mixed dietary fats during an energy-restricted diet: effects on weight loss, serum lipids, fibrinogen, and vascular function by Pieterse Z1, Jerling JC, Oosthuizen W, Kruger HS, Hanekom SM, Smuts CM, Schutte AE.(PubMed)

3. Avocado and Diabetes
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

Extracts of Persea americana Mill (Lauraceae) ("Avocado") has been used in folk medicine to treat hypertension and lower blood glucose, but the underlined  mechanism is unknown. According to University of KwaZulu-Natal, in STZ-induced diabetic rats, the extract may be used in diabetic management through its effectiveness in increased hepatic glycogen concentrations, decreased urine flow and electrolyte excretion rates, whilst subchronic treatment reduced plasma creatinine and urea concentrations(1). Other study suggested that consuming monounsaturated fatty acids in avocado in the diet of patients with non-insulin-dependent diabetes mellitus improves the lipid profile favorably, maintains an adequate glycemic control, and offers a good management alternative(2) and high-monounsaturated fat diet metabolited better in some aspects than the currently recommended diet for non-insulin-dependent diabetes mellitus (NIDDM)(3).


References
(1) Effects of Persea americana Mill (Lauraceae) ["Avocado"] ethanolic leaf extract on blood glucose and kidney function in streptozotocin-induced diabetic rats and on kidney cell lines of the proximal (LLCPK1) and distal tubules (MDBK), by Gondwe M1, Kamadyaapa DR, Tufts MA, Chuturgoon AA, Ojewole JA, Musabayane CT.(PubMed)
(2) Effect of a high-monounsaturated fat diet enriched with avocado in NIDDM patients by Lerman-Garber I1, Ichazo-Cerro S, Zamora-González J, Cardoso-Saldaña G, Posadas-Romero C.(PubMed)
(3) The high-monounsaturated fat diet as a practical alternative for NIDDM by Campbell LV1, Marmot PE, Dyer JA, Borkman M, Storlien LH.(PubMed)

4. Avocado and Cardiovascular disease
Heart diseases are caused by high blood pressure that contributes to hardening of the arteries. High levels of bad cholesterol (LDL) building up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.
In animal study,  Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) showed an significant effect in reduced risk and treatment of heart diseases, its hypotensive (antihypertensive) effects(1). According to Nutrition Science Solutions LLC, consumption of one-half an avocado (68 g), not only provided many nutrients which are necessary for body needed, but also supported cardiovascular health(2).
The National Health and Nutrition Examination Survey (NHANES) 2001-2008, suggested that avocado consumption is associated with improved overall diet quality, nutrient intake, and reduced risk of metabolic syndrome(3), including cardiovascular disease.

References
(1) Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals by Ojewole JA1, Kamadyaapa DR, Gondwe MM, Moodley K, Musabayane CT.(PubMed)
(2) Hass avocado composition and potential health effects by Dreher ML1, Davenport AJ.(PubMed)
(3) Avocado consumption is associated with better diet quality and nutrient intake, and lower metabolic syndrome risk in US adults: results from the National Health and Nutrition Examination Survey (NHANES) 2001-2008 by Fulgoni VL 3rd1, Dreher M, Davenport AJ.(PubMed)

5. Avocado and Anti inflammatory effect
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.
In UV-induced damage in skin cells, the unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, showed to reduce UVB-induced damage and inflammation in skin. Application of the extract  prior to their exposure to UVB enhanced a protective effect, increased cell viability, decreased the secretion of IL-6, a pro-inflammatory cytokine and an anti-inflammatory myokine. and PGE(2) in mediated the inflammation process , and DNA repair(1).
Avocado soybean unsaponifiables (ASU)supplement, when applied alone exhibited pain-reducing and anti-inflammatory effects, through suppressing TNF-alpha, a pleiotropic inflammatory cytokine, IL-1beta which plays a central role in the regulation of immune and inflammatory responses, COX-2 which  involved in the conversion of arachidonic acid to prostaglandin H2, iNOS gene expression which involved in immune response, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages(3). When used combination with epigallocatechin gallate, in the study by Nutramax Laboratories, Avocado soybean unsaponifiables (ASU)supplement demonstrated a significantly anti-inflammatory activity and may offer an attractive supplement or alternative to non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis(2).

References
(1) Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells by Rosenblat G1, Meretski S, Segal J, Tarshis M, Schroeder A, Zanin-Zhorov A, Lion G, Ingber A, Hochberg M.(PubMed)
(2) Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate by Heinecke LF1, Grzanna MW, Au AY, Mochal CA, Rashmir-Raven A, Frondoza CG.(PubMed)
(3) Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages by Au RY1, Al-Talib TK, Au AY, Phan PV, Frondoza CG.(PubMed)

6. Avocado and as Antioxidant
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
eEthyl acetate, containing 70% acetone, and 70% methanol extracts of the peel, pulp, and seed from two avocado (Persea americana Mill) exerted its antioxidant activity in vitro againstantimicrobial effects against Gram-positive bacteria through inhibition of oxidative stress(1). the Tecnológico de Monterrey-Campus Monterrey suggested that avocado pulp may sever as a novel lipophilic antioxidants in a food matrix due to the presence of acetogenins(2), a class of polyketide natural products found in plants. The University of California in the study of the effect of harvest date on nutritional compounds and antioxidant activity (AOC) in avocado (Persea americana Mill. cv Hass) fruit , suugested that AOC in early harvested fruit after storage for 35 days was much higher than that in late harvested fruit after storage for 21 days(3).

References
(1) Avocado (Persea americana Mill.) phenolics, in vitro antioxidant and antimicrobial activities, and inhibition of lipid and protein oxidation in porcine patties by Rodríguez-Carpena JG1, Morcuende D, Andrade MJ, Kylli P, Estévez M.(PubMed)
(2) Activity-guided identification of acetogenins as novel lipophilic antioxidants present in avocado pulp (Persea americana) by Rodríguez-Sánchez D1, Silva-Platas C, Rojo RP, García N, Cisneros-Zevallos L, García-Rivas G, Hernández-Brenes C.(PubMed)
(3) Effect of harvest date on the nutritional quality and antioxidant capacity in 'Hass' avocado during storage by Wang M1, Zheng Y, Khuong T, Lovatt CJ.(PubMed)


8. Avocado and osteoarthritis
Osteoarthritis is a group of diseases involved progressive denegation of joints, including articular cartilage and subchondral bone.
Avocado/soybean unsaponifiables (ASU) supplement, in the searching for randomised, placebo-controlled, double-blind trials of ASU, suggested that ASU improved the symptoms of OA, with only real long-term trial yielded a largely negative result, according to Dr. Ernst E.(1). The Frederiksberg Hospital in the study of the same, with 664 OA patients with either hip (41.4%) or knee (58.6%) suggested that the 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA(2). Other study also found a significantly effective of the supplement ASU in reduced the progression of joint space loss as compared with placebo in the subgroup of patients with advanced joint space narrowing, but require confirmation in a larger placebo-controlled study in hip OA(3).

References
(1) Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review by Ernst E.(PubMed)
(2) Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials by Christensen R1, Bartels EM, Astrup A, Bliddal H.(PubMed)
(3) Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip by Lequesne M1, Maheu E, Cadet C, Dreiser RL.(PubMed)

9. Avocado and Prostate Cancer
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae.
Nutrients
1. Vitamin K
2. Dietary fiber
3. Vitamin B6
4. Vitamin C
5. Folate
6. Copper
7. Potassium
8. Amino acid
9. Others
a) Vitamin A
b) Vitamin B1, B2, B3, B12
c) Vitamin D
d) Vitamin E
e) Carotenoid
f) Pantothenic acid
g) Calcium
h) Chromium
Chemical constituents
The fruit contains campesterol, high amounts of β-sitosterol (average 76.4 mg/100 g); fatty acids (approximately 60% monounsaturated, 20% saturated, and 20% unsaturated); high amounts of glutathione (27.7 mg/100 g); approximately 2% protein; 6–9% carbohydrates and sugars (glucose, fructose, d-mannoheptulose, a taloheptulose, and an alloheptulose); two bitter substances (1-acetoxy-2,4-dihydroxyheptadeca-16-ene and 1,2,4-trihydroxyheptadeca-16-ene); carnitine; proanthocyanidins; persenones A and B(a).
Intake of dietary MUFA from whole fruit of avocado are associated to reduced risk of prostate cancer, the new stdy at the University of the West Indies suggested(1). In support of the above, the University of California suggested that the anti prostate cancer effect are not as result of a single ingredient such as related carotenoids (zeaxanthin, alpha-carotene, and beta-carotene), lutein but the interaction of all ingredients in the whole fruit conbination with other det-derived phytochemicals through cell cycle arrest and  G(2)/M cell cycle arrest accompanied by an increase in p27 protein in controlling the cell cycle progression at G1 in incubation of PC-3 cells(3). The Purdue University study in the evaluation of the anti cancers effect of avocado showed  a positive effect of the whole fruit in inhibition of six human tumor cell lines in culture, including human prostate adenocarcinoma (PC-3) cells(4).

References
(a) Leung's Encyclopedia of Natural Ingredients:Chemical Composition of Avocado
(1) Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica by Jackson MD1, Walker SP, Simpson-Smith CM, Lindsay CM, Smith G, McFarlane-Anderson N, Bennett FI, Coard KC, Aiken WD, Tulloch T, Paul TJ, Wan RL.(PubMed)
(2) Inhibition of prostate cancer cell growth by an avocado extract: role of lipid-soluble bioactive substances. by Lu QY1, Arteaga JR, Zhang Q, Huerta S, Go VL, Heber D.(PubMed)
(3) Cytotoxic and insecticidal constituents of the unripe fruit of Persea americana by Oberlies NH1, Rogers LL, Martin JM, McLaughlin JL.(PubMed)

10. Avocado and Breast cancer
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae.
Nutrients
1. Vitamin K
2. Dietary fiber
3. Vitamin B6
4. Vitamin C
5. Folate
6. Copper
7. Potassium
8. Amino acid
9. Others
a) Vitamin A
b) Vitamin B1, B2, B3, B12
c) Vitamin D
d) Vitamin E
e) Carotenoid
f) Pantothenic acid
g) Calcium
h) Chromium
Chemical constituents
The fruit contains campesterol, high amounts of β-sitosterol (average 76.4 mg/100 g); fatty acids (approximately 60% monounsaturated, 20% saturated, and 20% unsaturated); high amounts of glutathione (27.7 mg/100 g); approximately 2% protein; 6–9% carbohydrates and sugars (glucose, fructose, d-mannoheptulose, a taloheptulose, and an alloheptulose); two bitter substances (1-acetoxy-2,4-dihydroxyheptadeca-16-ene and 1,2,4-trihydroxyheptadeca-16-ene); carnitine; proanthocyanidins; persenones A and B(a).
Persin, the toxin chemical compound found in the fruits and leaves of avocado showed to inhubut huamn breast cancer cell line, inthe testing of synthetic analogues of the avocado-produced toxin persin(1). In support to the above, researchers at the Gavan institution, suggested that persin could be given together with commonly used breast cancer drugs like tamoxifen, which seem to act in a different way, patients would benefit by needing smaller amounts of each type of medicine. Indeed, in the laboratory, persin and tamoxifen look to be a good combination(2). Other member of Persea, Persea declinata (Bl.) Kosterm is a member from the same genus with avocado, in  the Lauraceae family, widely distributed in Southeast Asia, in the testing against MCF-7 Cells showed that its bark methanolic crude extract (PDM) found to inhibit cell cycle arrest and subsquently induced apoptosis through increased the expression of the proapoptotic molecule, Bax(pro-apoptosis), but decreased the expression of prosurvival proteins, Bcl-2 (pro-apoptotic oranti-apoptotic) and Bcl-xL(pro- and anti-survival protein) in a dose-dependent manner(3).

Side effects1. Skin product of avocado oils may contain latex which can cause skin side effect in certain people with hypersensitivity to latex, leading to symptoms of reddening of the skin, itching, hives, or eczema.
2. Liver damage
Certain types of avocado may cause liver damage as a result of collagen accumulation in the liver
3. Breastfeeding
Some types of Avocado may be unsafe during breastfeeding as it can cause problems of upset stomachs in babies.
4. Drugs
Avocado may decrease the effect of "blood thinning" or anti-inflammatory medications.
5. It may cause symptoms of gastrointestinal irritation, vomiting, diarrhoea, respiratory distress, congestion, fluid accumulation due to toxic fatty acid derivative, Persin.
6. Etc.

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References
(a) Leung's Encyclopedia of Natural Ingredients:Chemical Composition of Avocado
(1) Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R)-persin in human breast cancer cells by Brooke DG1, Shelley EJ, Roberts CG, Denny WA, Sutherland RL, Butt AJ.(PubMed)
(2) Persin - the avocado toxin that kills breast cancer cells(Gavan Institution)
(3) Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation by Narrima P1, Paydar M1, Looi CY1, Wong YL1, Taha H2, Wong WF3, Ali Mohd M1, Hadi AH(PubMed)

11. 12. Avocado and Skin health
In a in growing rats fed diets containing 10% (w/w) of the tested oils, showed to increased soluble collagen content due to a result of a consequence of the inhibition of lysyl oxidase activity(1). On wound healing in rats, after  the 14th day of treatment with 50% SSFAO or avocado oil containing rich source of oleic acid and essential fatty acids, exhibited a significant increase in percentage wound contraction and reepithelialisation(2). In Exposing skin to ultraviolet (UV) radiation, unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, reduced significantly UV-induced cellular damage, through increasing cell viability, decreased the secretion of IL-6, a pro-inflammatory cytokine and an anti-inflammatory myokine. and PGE(2) in mediated the inflammation process(3).

References
(1) The effect of various avocado oils on skin collagen metabolism by Werman MJ1, Mokady S, Nimni ME, Neeman I.(PubMed)
(2) Effect of semisolid formulation of persea americana mill (avocado) oil on wound healing in rats by de Oliveira AP1, Franco Ede S, Rodrigues Barreto R, Cordeiro DP, de Melo RG, de Aquino CM, E Silva AA, de Medeiros PL, da Silva TG, Góes AJ, Maia MB.(PubMed)
(3) Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells by Rosenblat G1, Meretski S, Segal J, Tarshis M, Schroeder A, Zanin-Zhorov A, Lion G, Ingber A, Hochberg M.(PubMed)

Herbal Cinnamon and Infertility

Cinnamon, a kitchen spicy in many cultures, may been best known for its effect in reduced levels of blood glucose in diabetics and lipid peroxidation through its antioxidant activity(4) . Its underline mechanisms in enhancing fertility in patient with yang deficiency are unknown.

Infertility is defined as the inability of a couple to conceive after 12 months of unprotected sexual intercourse or the cannot carry the pregnancy full term. It affects over 5 million couples alone in the U. S. and many times more in the world. Because of an unawareness of treatments, only 10% seek help from professional specialists. In fact, about 35% of infertility is caused by the male's inability to fertilize. 35% is caused by the female's inability to conceive, 10% attributes to both, and 10 % is considered a failure with an unknown cause.

A 45 women randomized, 26 women completed 3 months of the study, and 17 women completed the entire 6 months of the study, with Polycystic Ovary Syndrome, showed a positive effect in improvement of menstrual cyclicity associated to Luteal phase progesterone levels and ovulatory menses without altering insulin resistance or serum androgen levels(1). Cinnamaldehyde, a major chemical compound of cinnamon, also shoed to enhance fertility through selectively induced progesterone production and inhibited production of testosterone and dehydroepiandrosterone in human adrenal cells(3).

Its extract in PCOs study not only showed to reduce insulin resistance in vitro and in vivo studies by increasing phosphatidylinositol 3-kinase activity in the insulin signaling pathway, but also improved menstrual cyclicity through significant reductions in insulin resistance(8).

In infertile male rat study conducted by Fırat University, long-term cinnamon bark oil(CPO) improved the effect on testicular oxidant-antioxidant balance and sperm quality with significantly decreasing the abnormal sperm rate and apoptotic germ cell count(2).
The study in male rat reproductive system induced carbon tetrachloride (CCl4 ), the cinnamon bark oil(CPO), also showed a significant improvements in absolute weights of testis and epididymis, all sperm quality parameters, LPO level, apoptotic index and testicular(6)

Taken altogether, Cinnamon may be effective in promoting fertility in both sexes through enhancing the menstrual cycle in women and improving sperm performance in men. Unfortunately, according to DR. Georgakopoulou EA(6),  Oral intake of Cinnamon may cause Stomatitis, and burning sensation in mouth with large amount. The traditional Chinese medicine also insisted that Overdoses of cinnamon can be toxic and damaged to liver(5).

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References
(1) Preliminary Evidence that Cinnamon Improves Menstrual Cyclicity in Women with Polycystic Ovarian Syndrome: a Randomized Controlled Trial by Kort DH1, Lobo RA.(PubMed)
(2) Effects of cinnamon (Cinnamomum zeylanicum) bark oil on testicular antioxidant values, apoptotic germ cell and sperm quality by Yüce A1, Türk G, Çeribaşi S, Sönmez M, Çiftçi M, Güvenç M.(PubMed)
(3) Selective stimulation by cinnamaldehyde of progesterone secretion in human adrenal cells by Iwaoka Y1, Hashimoto R, Koizumi H, Yu J, Okabe T.(PubMed)
(4) Preventive effect of cinnamon essential oil on lipid oxidation of vegetable oil by Keshvari M1, Asgary S, Jafarian-Dehkordi A, Najafi S, Ghoreyshi-Yazdi SM(PubMed)
(5) Popular #Herbs - #Dang Qui (Angelica sinensis)
(6) Chromium and polyphenols from cinnamon improve insulin sensitivity by Anderson RA.(PubMed)
(7) Effectiveness of cinnamon (Cinnamomum zeylanicum) bark oil in the prevention of carbon tetrachloride-induced damages on the male reproductive system by Yüce A1, Türk G, Çeribaşı S, Güvenç M, Çiftçi M, Sönmez M, Özer Kaya Ş, Çay M, Aksakal M.(PubMed)
(8) The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study by Wang JG1, Anderson RA, Graham GM 3rd, Chu MC, Sauer MV, Guarnaccia MM, Lobo RA.(PubMed)

Wednesday, May 14, 2014

Dang Qui and Menopausal Symptoms

Most women living in West entering the stage of peri menopause onward, may experience certain menopausal symptoms due to the reduced production of certain steroid hormones because of aging.
According to the statistic, approximately 70% of menopausal women are experience some kinds of symptoms such as hot flash, vaginal dryness, problem sleeping, mood swing, etc. but only 10% in the East. Some researchers suggested that this may be resulted of social and cultural structure difference and dietary habits.
The Good
Dang Qui or Chinese Angelica, the Queen of all herbs, according to Chinese medical literature, may be the next single herb or used conjunction with other herbs which may be comparable to hormonal therapies in alleviating the symptoms of menopause with little or no adverse effects, through its effectiveness in balancing the body hormones, even in case of depletion(1).

According to the University of Messina, in ovariectomized rats study, Dang Qui extract exhibited estrogenic activity in relieving climacteric symptoms through stimulation of the uterine histoarchitecture, a significant cornification in the vaginal epithelium and a reduction of serum LH concentration(2).
Danggui Buxue Tang (DBT) containing Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui) is a simple decoction, having about 800 years of usage in China to treat menopausal irregularity in women, suggested that the effectiveness of the formula may be depended on the crucial factors of extraction time and number of repeats of the extraction(6).
EstroG-100, a herbal extract containing Cynanchum wilfordii, Phlomis umbrosa and Angelica gigas has shown to alleviate the symptoms of vasomotor, paresthesia, insomnia, nervousness, melancholia, vertigo, fatigue and rheumatic pain in 12 weeks with 64 pre-, peri- and postmenopausal White Hispanic, White non-Hispanic and African American women(3).

The bad and Ugly
Unfortunately, The Chinese University of Hong Kong, in the testing of the effectiveness of Dang Qui used for peri- or postmenopausal relief, on the proliferation of estrogen receptor-positive (MCF-7) and negative (BT-20) breast cancer cells in vitro, suggested that he water extract of dong quai stimulated the growth of MCF-7 cells, possibly dependent of weak estrogen-agonistic activity, and augmented the BT-20 cell proliferation independent of estrogen receptor-mediated pathway(4) and the ferulic acid (FA), an active compound derived from Angelica sinensis may cause human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression(9).  Conflict to the above, the Chung Shan Medical University Hospital study, indicated that A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment(8).

 Dr. Low Dog T., told PubMed "Dang Qai, extract, showed insignificant effective in ameliorating menopausal symptoms in dose depending manner", in the review of total of 19 studies met the inclusion criteria(5), and Dong quai [Angelica sinensis (Oliv.) Diels] showed only weak ER binding and PR, according to the University of Illinois at Chicago(6).

Taken altogether, without going into reviews, Dang Qui and herbal formula containing the herb may be effective in relieving menopausal symptoms. Menopausal women with history of breast cancer or carried gene mutation Her2, should not take the herb without consulting to their doctors & Related field specialist. As always, all articles written by Kyle J. Norton are for information & education only.
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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html


References
(1) Popular #Herbs - #Dang Qui (Angelica sinensis)
(2) Estrogenic activity of standardized extract of Angelica sinensis by Circosta C1, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F.(PubMed)
(3) The effect of herbal extract (EstroG-100) on pre-, peri- and post-menopausal women: a randomized double-blind, placebo-controlled study by Chang A1, Kwak BY, Yi K, Kim JS.(PubMed)
(4) Use of dong quai (Angelica sinensis) to treat peri- or postmenopausal symptoms in women with breast cancer: is it appropriate? by Lau CB1, Ho TC, Chan TW, Kim SC.(PubMed)
(5) Menopause: a review of botanical dietary supplements by Low Dog T.(PubMed)
(6) Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: orthogonal array design to optimize the extraction of chemical constituents by Song ZH1, Ji ZN, Lo CK, Dong TT, Zhao KJ, Li OT, Haines CJ, Kung SD, Tsim KW.(PubMed)
(7) Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms by Liu J 1, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL.(PubMed)
(8) Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients by Zhuang SR1, Chiu HF, Chen SL, Tsai JH, Lee MY, Lee HS, Shen YC, Yan YY, Shane GT, Wang CK.(PubMed)
(9) Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells by Chang CJ1, Chiu JH, Tseng LM, Chang CH, Chien TM, Wu CW, Lui WY.(PubMed)

Apricot and Plum, the next Generation of Oral Hygiene

Kyle J. Norton(Draft Article)

People with problem of oral hygiene may consider to add Apricot and Plum into their diet, new study suggested. In fact, the foods not contain measurable amount of nutrients which are important to
maintain the proper growth and body functions, but also enhance the immune system in fighting against invasion of  foreign substances, including bacterial and viral agents.

Patients oral hygiene incompetence may be experience certain dental consequences such as  gums diseases  including cavities or even tooth loss.

According to the study by the University of Karachi, butanolic extract from Prunus armeniaca exhibited antibacterial activity against both Gram positive and Gram negative bacteria(1).

Mei, other member of the Prunus armeniaca, a favor snack of Asian women, especially for those in the early stage of pregnancy, probably due to its sour taste, is also found to improve oral hygiene. According to the study of the University of Hong Kong, in the differentiation of the anti bacterial effectiveness of 20 traditional Chinese herbs. Mei was found to exert a significant effect against all for testing oral bacteria, namely, Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis(3).

Organic acids, the main ingredient of fructus mume extract, also showed a strong evidence in enhancing oral hygiene through its antimicrobial effect on orthodontic bracket in vitro by increasing the amount of dead bacteria on the surface(4).

Mei or Lu E Mei is also known as Plum. The sour and warm herb has been used in TCM to treat  diarrhea, pain from colic caused by ascaris, alleviates thirst, as well as other digestive system diseases caused by imbalance of  bacteria. According to the the University of Hong Kong, at suspension of 2 g/mL, the extract showed a significantly inhibited effect on all tested oral pathogenic bacteria and may be considered as a potential anti- oral antimicrobial agent to control or prevent dental diseases(5).

Unfortunately, accompanied to their health effects, Mei can not be used in case of internal heat excess  such as high fever with infection or cold or flu without sweat)(6) and sulfite sensitive People  should not consume fried apricot because sulfur- compounds are often added to dried foods as preservatives to prevent them from oxidation, according to traditional Chinese medicine.(7).

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References
(1) Flavonoid glycosides from Prunus armeniaca and the antibacterial activity of a crude extract by Rashid F1, Ahmed R, Mahmood A, Ahmad Z, Bibi N, Kazmi SU.(PubMed)(2)
(3) Antimicrobial activity of Chinese medicine herbs against common bacteria in oral biofilm. A pilot study by Wong RW1, Hägg U, Samaranayake L, Yuen MK, Seneviratne CJ, Kao R.(PubMed)
(4) The antimicrobial efficacy of Fructus mume extract on orthodontic bracket: a monospecies-biofilm model study in vitro by Chen Y1, Wong RW, Seneviratne CJ, Hägg U, McGrath C, Samaranayake LP, Kao R.(PubMed)
(5) Prunus mume extract exhibits antimicrobial activity against pathogenic oral bacteria by Seneviratne CJ1, Wong RW, Hägg U, Chen Y, Herath TD, Samaranayake PL, Kao R.(PubMed)
(6)
(7) #Healthy #Foods - Fruits - Apricot (Prunus armeniaca)
(8) Chinese Herbs – Mei or Lu E Mei (Fructus Armeniaca mume)

Tuesday, May 13, 2014

Herbal Cinnamon and Diabetes

 Kyle J. Norton(Draft Article)

Cinnamon, a kitchen spicy in many cultures, may have gained many believers, including medical professions because of its anti diabetic effect, through regulating the blood glucose levels in healthy and diabetic subjects. According to herbalists, intake of 1/4 tsp. in the morning and evening may reduce the blood sugar significantly with little or no adverse side effects.

The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.(1).

According to the 2011 statistic from National Diabetes InformationClearinghouse (NDIC), among U.S. residents ages 65 years and older, 10.9 million, or 26.9 percent, had diabetes in 2010, about 215,000 people younger than 20 years had diabetes—type 1 or type 2—in the United States in 2010 and approximately,  1.9 million people ages 20 years or older were newly diagnosed with diabetes in 2010 in the United States.

In a total of 66 patients with type 2 diabetes study conducted by Xuhui District Central Hospital, showed a reduction significant of blood triglyceride levels were also significantly reduced in the low-dose group, after 3 months of oral administration(2)

Some researchers suggested that although cinnamon extract improved fasting blood glucose levels and glucose tolerance without altering the insulin secretion, through  lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues(3).

Dr. Kim SH and Dr. Choung SY. told PubMed that "the effect of cinnamon in significantly increases insulin sensitivity, reduces serum, and hepatic lipids, and improves hyperglycemia and hyperlipidemia possibly by regulating the PPAR-medicated glucose and lipid metabolism"(4)

In support of the above, chromium(Cr) and polyphenols found in cinnamon (Cinnamomon cassia) indicated a improvement of glucose, insulin, cholesterol and HbA1c  in patients with type 2 diabetes following Cr supplementation, in a double-blind placebo-controlled study(7).

Unfortunately, according to the Western University of Health Sciences, consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, but insisted that high degree of heterogeneity may limit the ability to apply these results to patient care, due to the unclear preferred dose and duration of therapy(5)

 A randomized clinical trial in which 70 Patients with type II diabetes assigned randomly two groups (35 in cinnamon and 35 in placebo group for the testing of  the effect of cinnamon on the glucose level in blood, indicated an insignificant effect of using cinnamon on glucose level of diabetic patients and the herb should not be recommended to patients with type II diabetes depending on further studies(6).

Taken altogether, cinnamon in low dose may be effective in controlling the levels of blood glucose in patient with diabetes without altering the insulin level. according to DR. Georgakopoulou EA(7),  Oral intake of Cinnamon may cause Stomatitis, and burning sensation in mouth with large amount. The traditional Chinese medicine also insisted that Overdoses of cinnamon can be toxic and damaged to liver(1).

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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
 

References
(1) @Popular Herbs -Cinnamon
(2) Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes by Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y.(PubMed)
(3) Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity by Sartorius T1, Peter A2, Schulz N3, Drescher A2, Bergheim I4, Machann J5, Schick F6, Siegel-Axel D2, Schürmann A3, Weigert C1, Häring HU1, Hennige AM(PubMed)
(4) Antihyperglycemic and antihyperlipidemic action of Cinnamomi Cassiae (Cinnamon bark) extract in C57BL/Ks db/db mice by Kim SH1, Choung SY.(PubMed)
(5) Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis by Allen RW1, Schwartzman E, Baker WL, Coleman CI, Phung OJ.(PubMed)
(6) The Effect of Cinnamon on Glucose of Type II Diabetes Patients by Hasanzade F1, Toliat M2, Emami SA3, Emamimoghaadam Z(PubMed)
(7) Chromium and polyphenols from cinnamon improve insulin sensitivity by Anderson RA.(PubMed)

Monday, May 12, 2014

Whole food Papaya and Diabetes

Kyle J,Norton(Draft Article)

People with Type II Diabetes may be thinking to adding whole food papaya into their diet. the recent study suggested(1) ,
The finding not only showed the effectiveness of unripe pawpaw fruit (Carica papaya) in inhibition α-amylase, α-glucosidase, but also induced lipid peroxidation in a dose-dependent manner, in rat pancreas(1).
The key enzymes of α-amylase, α-glucosidase, involved in the digestion of carbohydrates, have been linked to onset of type 2 diabetes. Inhibition of these enzymes can significantly reduce the post-prandial increase of blood glucose and have been considered by therapists in use for management of blood glucose level in type 2 diabetic and borderline patients(2).

In streptozotocin-induced diabetic rats study, the aqueous extract of leaves of C. papaya administered strongly controlled blood glucose levels(3), through prevention of hepatocyte disruption, as well as accumulation of glycogen and lipids via its hypoglycemic and antioxidant effect(4)

Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

In a new study, the researchers at the Davis Heart and Lung Research Institute, fermented papaya preparation as was tested whether it improves dermal wound healing outcomes in adult diabetic mice by preventing the  risk of infections(5).
The result was astonishing, the fermentation not only up regulated the Sp1 DNA binding activity(modulating the cellular response to DNA damage) in Peripheral blood mononuclear cells (PBMC) but also the protein and mRNA expression of Rac2(regulates a number of cellular functions)(5).

A randomized controlled clinical trial conducted at the Cardiac Centre, ANDI Centre of Excellence for Biomedical and Biomaterials Research and Department of Biosciences University of Mauritius, suggested that oral administration of 6g FPP®/day for a period of 14 weeks could improve the general health status of several organs targeted by oxidative stress during diabetes and suggested that the supplement may be used in the management the complications of diabetes such as cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress(6).

Taken altogether, Papaya unripe, fermented papaya and leaves may be effective in diabetic management  through controlling the levels of glucose and  reduced risk of complication.

Some Western researchers insisted that large sample size and multi center studies are necessary to validate its effectiveness by identifying the ingredients which are comparable to recently pharmaceutical medicine in use because geography, environment, time of harvest, etc. may influence the concentration of the food cultivation.
 In fact, herbalists have long acknowledged that the external factors (mentioned above) may alter the quality of the herbs and foods by classifying these difference either through price or formula differentiation. In deed, the effectiveness with little or no adverse side effects of the formula is not the concentration of individual herb and a herb itself but the interaction of all ingredients in a herb and herbs in the same formula. Withdrawing only one ingredient of the herb in treating certain diseases may be effective but enhanced complicative consequences. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html

References
(1) Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water-extractable phytochemicals from unripe pawpaw fruit (Carica papaya) by Oboh G, Olabiyi AA, Akinyemi AJ, Ademiluyi AO.(PubMed)
(2) Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update by Tundis R1, Loizzo MR, Menichini F.(PubMed)
(3) Antihyperglycemic and hypolipidemic activities of aqueous extract of Carica papaya Linn. leaves in alloxan-induced diabetic rats by Maniyar Y, Bhixavatimath P.(PubMed)
(4) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats by Juárez-Rojop IE1, Díaz-Zagoya JC, Ble-Castillo JL, Miranda-Osorio PH, Castell-Rodríguez AE, Tovilla-Zárate CA, Rodríguez-Hernández A, Aguilar-Mariscal H, Ramón-Frías T, Bermúdez-Ocaña DY.(PubMed)
(5) Correction of aberrant NADPH oxidase activity in blood-derived mononuclear cells from type II diabetes mellitus patients by a naturally fermented papaya preparation by Dickerson R1, Deshpande B, Gnyawali U, Lynch D, Gordillo GM, Schuster D, Osei K, Roy S.(PubMed)
(6) Effects of a short term supplementation of a fermented papaya preparation on biomarkers of diabetes mellitus in a randomized Mauritian population by Somanah J1, Aruoma OI, Gunness TK, Kowelssur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J, Bourdon E, Bahorun T.(PubMed)

Saturday, May 10, 2014

Herbal Ginseng and Erectile Dysfunction

 Kyle J. Norton(Draft Article)

In finding a whole food and herb, comparing to the presently pharmaceutical medicine in use with little and no adverse effect(4), scientific communities have looking into herbal ginseng which has been used extensively in traditional Chinese medicine for treatment of sexual dysfunction of both sex.

According to statistic, in US alone, more than18 Million Men over 20 of ages are affected by Erectile Dysfunction and approximately 5% of 40-year-old men and between 15% and 25% of 65-year-old men experience ED on a long-term basis)National Institutes of Health). Astonishingly, lifetime use of ED medications was reported by 24% of men. Almost 69% of ED medication users reported obtaining ED medications from a physician. Fifty-nine percent of ED medication users reported taking the medications to enhance their sexual experience rather than to treat ED, which was marginally associated with stimulant use. according to Department of Veterans Affairs Puget Sound Health Care System, Seattle(1).

In comparison of the effect of erectile dysfunction with diabetes and men with erectile dysfunction due to other causes study indicated that the diseases not only affect Sexual Experience-Psychological Impact domains but also Emotional Life-Psychological Impact domain(2).

Ginseng, the King of Chinese herb, according to the literature in Chinese medicine found by Emperor Shen-Nung, the second of China's mythical emperors (3500-2600 BCE), through his treatise 'Shen Nung Benchau Jing', expressed the efficacy of herbal ginseng well being as a resemblance of human form and its rejuvenative and aphrodisiac properties. The use of ginseng for erectile dysfunction by Emperor Shen-Nung was unique for its time. It continues to hold parallels as a modern-day herbal aphrodisiac 5000 years on(3).

Panax notoginseng saponins (PNS), a major ingredient found in ginseng,  in the study of erectile dysfunction and the underlying mechanism by using a rat diabetic erectile dysfunction model in diabetic rat, showed a positive effect in deduction of oxidative stress cause of erectile dysfunction and and restored functions of endothelial cells and smooth muscle cells in the penis, through reduced level of malondialdehyde and increased levels of superoxide dismutase, glutathione and Akt(5) and possibly via the NO/cGMP pathway and restores the function of endothelium in corpus cavernosum(6).

In root-derived Korean red ginseng (KRG; Panax ginseng) study, researchers at the Yonsei University College of Medicine, found that GB0710  relax the penile corpus cavernosum smooth muscle (CCSM), through ntracellular NO production in human microvascular endothelial cells by  N(G)-monomethyl-L-arginine induction and inhibition(7).

In a 119 men with mild-to-moderate ED participated in a multicenter, randomized, double-blind, parallel, placebo-controlled clinical study, oral administration of the SKGB extract improved all domains of sexual function(8)(9).

According to Chinese medicine has been prescribed ginseng over 5000 years of history to promote yang and to improve cardiac function, short of breath, blood pressure. Panax ginseng can generates fluids and reduce thirst, to treat anxiety, insomnia, dizziness/headache, forgetfulness, impotence, diabetes, bleeding in the vagina not during period, etc.

Dr. Shergis JL and the researcher team at the School of Health Sciences and Health Innovations Research Institute-HIRi, RMIT University, told PubMed " Overall, the quality of Panax ginseng (andomized controlled trials ) RCT methodology has improved since the CONSORT checklist was introduced. However, more can be done to improve the methodological quality of, and reporting in, RCTs"(10)

But the use of herbal medicine in treating erectile dysfunction should be taken with care. Dr Ho CC and Dr. Tan HM. said" Many herbal therapies appear to have potential benefits, and similarly, the health risks of various phytotherapeutic compounds need to be elucidated. Properly designed human trials should be worked out and encouraged to determine the efficacy and safety of potential phytotherapies"(11). As the herb has shown mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation in dose depending manner(12).

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Reference
(1) Erectile dysfunction medication use among men seeking substance abuse treatment.
Horvath KJ, Calsyn DA, Terry C, Cotton A.(PubMed)
(2) Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database by Penson DF, Latini DM, Lubeck DP, Wallace KL, Henning JM, Lue TF; Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database(PubMed
(3) The history of ginseng in the management of erectile dysfunction in ancient China (3500-2600 BCE) by Nair R, Sellaturay S, Sriprasad S.(PubMed
(4) Erectile dysfunction: Viagra and other oral medications(Mayo clinic)
(5) Panax notoginseng Saponins Improve Erectile Function through Attenuation of Oxidative Stress, Restoration of Akt Activity and Protection of Endothelial and Smooth Muscle Cells in Diabetic Rats with Erectile Dysfunction by Li H, He WY, Lin F, Gou X.(PubMed)
(6) Panax notoginseng saponins improve the erectile dysfunction in diabetic rats by protecting the endothelial function of the penile corpus cavernosum by Lin F, Gou X.(PubMed
(7) Effects of Korean ginseng berry extract (GB0710) on penile erection: evidence from in vitro and in vivo studies by Cho KS, Park CW, Kim CK, Jeon HY, Kim WG, Lee SJ, Kim YM, Lee JY, Choi YD.(PubMed
(8) Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study by Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, Lee SJ, Chung WS(PubMed
(9) Effects of tissue-cultured mountain ginseng (Panax ginseng CA Meyer) extract on male patients with erectile dysfunction by Kim TH, Jeon SH, Hahn EJ, Paek KY, Park JK, Youn NY, Lee HL.(PubMed) 
(10) Quality and risk of bias in Panax ginseng randomized controlled trials: a review by Shergis JL, Zhang AL, Zhou W, Xue CC.(PubMed)
(11) Rise of herbal and traditional medicine in erectile dysfunction management by Ho CC, Tan HM.(PubMed)
(12) Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers by Lee NH, Yoo SR, Kim HG, Cho JH, Son CG.(PubMed)